Investigating the connection among thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents affected by type 1 diabetes.

OBJECTIVES: A connection between thyroid hormones (THs) and diverse metabolic pathways has been reported. We evaluated thyroid function and tissue sensitivity to THs in children and adolescents with T1D in comparison to euthyroid controls. Additionally, we investigate whether a relationship exists between sensitivity indices and metabolic parameters. METHODS: A retrospective analysis was conducted on 80 pediatric patients diagnosed with T1D. Clinical parameters, TSH, FT3, FT4, and the presence of MS were documented. Additionally, indices of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were assessed. Thirty healthy subjects were considered as controls. RESULTS: The overall prevalence of MS was 7.27 %, with MS identified in 8 out of 80 (10 %) T1D subjects; none of the controls manifested MS (p<0.01). No significant differences were observed in indexes of tissue sensitivity to THs between subjects with or without MS (all p>0.05). Correlations between THs and indexes of THs tissue sensitivity and metabolic parameters in controls and T1D patients were noted. CONCLUSIONS: This study affirms a heightened prevalence of MS in children with T1D compared to controls and underscores the potential role of THs in maintaining metabolic equilibrium.

Epidemiology of growth hormone deficiency in children and adolescents: a systematic review.

OBJECTIVE: Growth hormone deficiency (GHD) is the most common pituitary hormone deficiency and is one of the main causes of short stature in children and adolescents. The aim of this study is to evaluate the epidemiology of pediatric GHD worldwide, since no other systematic review has been published so far. METHODS: We searched PubMed, Embase, and Web of Science up to July 2023 to find epidemiological studies involving children with GHD. Two review authors independently screened articles, extracted data and performed the quality assessment. RESULTS: We selected 9 epidemiological studies published from 1974 to 2022. The range of prevalence was 1/1107-1/8,646. A study based on a registry of GH users in the Piedmont region (Italy) reported the highest mean prevalence. In the included studies, the mean incidence ranged from 1/28,800 to 1/46,700 cases per year. One study reported a 20-year cumulative incidence of 127/100,000 for boys and 93/100,000 for girls. Studies were heterogeneous in terms of population (age and GHD etiology) and diagnostic criteria. As for the methodological quality of included studies, all but one study satisfied the majority of the checklist items. CONCLUSIONS: The included studies are mostly European, so the provided estimates cannot be considered global. International multicentre studies are needed to compare epidemiological estimates of GHD among different ethnical groups. Considering the considerable cost of human recombinant GH, the only available therapy to treat GHD, understanding accurate epidemiological estimates of GHD in each country is fundamental for resource allocation.

Corrigendum: Newborn screening for X-linked adrenoleukodystrophy in Italy: diagnostic algorithm and disease monitoring.

[This corrects the article DOI: 10.3389/fneur.2022.1072256.].

Glucometrics and device satisfaction in children and adolescents with type 1 diabetes using different treatment modalities: A multicenter real-world observational study.

AIMS: To analyze metabolic outcomes, diabetes impact and device satisfaction in children and adolescents with type 1 diabetes in Italy who used different treatment modalities for diabetes care in a real-life context. METHODS: In this multicenter, nationwide, cross-sectional study, 1464 participants were enrolled at a routine visit. The following treatment modalities were considered MDI + SMBG; MDI + CGM; Sensor Augmented Pump Therapy; predictive management of low glucose; Hybrid Closed Loop (HCL); Advanced Hybrid Closed Loop (AHCL). Health related quality of life was evaluated by the Italian version of the Diabetes Impact and Device Satisfaction Scale (DIDS) questionnaire. RESULTS: Patients treated with AID systems were more likely to have HbA1c ≤ 6.5 %, higher percentage of time with glucose levels between 70 and 180 mg/dL, lower percentage of time with glucose levels above 180 mg/dL, higher device satisfaction, and reduced impact of diabetes. All the therapeutic modalities with respect to MDI + CGM, except for MDI + SMBG, contributed to increase the device satisfaction. HCL and AHCL respect to MDI + CGM were associated with lower diabetes impact. CONCLUSION: Real-life use of automated insulin delivery systems is associated with reduced type 1 diabetes impact, increased device satisfaction, and achievement of glycemic goals.

Central Precocious Puberty in Italian Boys: Data From a Large Nationwide Cohort.

CONTEXT: There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. OBJECTIVE: We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. METHODS: We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. RESULTS: The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. CONCLUSION: In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.

Recurrent upper respiratory tract infections in early childhood: a newly defined clinical condition.

BACKGROUND: Recurrent Upper Respiratory Tract Infections (R-URTIs) pose a significant challenge in pediatric healthcare, affecting both children and their families. This study aimed to investigate the prevalence, risk factors, and clinical implications of R-URTI in children aged 0-5 years. METHODS: This observational study involved a sample of 483 children aged 0-5 years, focusing on establishing a practical and dynamic definition of R-URTI. Family pediatricians prospectively collected socio-demographic information, medical history, and recorded the occurrence of URTI episodes. Children were followed from recruitment until March 2021, predating the COVID-19 outbreak. RESULTS: A substantial prevalence of R-URTIs was found, estimating it at 5-10% among this age group. To define R-URTI, a practical and dynamic criterion was proposed: children experiencing a minimum of four URTI episodes, each lasting four days or more, within a six-month period, with intervals of well-being in between. CONCLUSIONS: The study highlighted that specific risk factors for R-URTI were elusive, suggesting that this condition may affect children regardless of their family or clinical history. Moreover, the study's stratification by age group and times of observation facilitated patient-specific clinical decision-making. The proposed definition may represent a valuable tool for clinicians in diagnosing and addressing R-URTI cases.

Safety, Metabolic and Psychological Outcomes of Medtronic MiniMed 780G™ in Children, Adolescents and Young Adults: A Systematic Review.

The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of an MD-Logic artificial pancreas algorithm. The system may deliver automatic correction boluses up to every 5 min, and it allows the user to choose between three glucose target setpoints (100, 110 and 120 mg/dL). We aimed to review the current evidence on this device in children, adolescents, and young adults living with type 1 diabetes. We screened 783 papers, but only 31 manuscripts were included in this review. Data on metabolic outcomes show that this system is safe as regards severe hypoglycaemia and diabetic ketoacidosis. The glycated haemoglobin may drop to levels about 7%, with CGM reports showing a time in range of 75-80%. The time above range and the time below range are within the recommended target in most of the subjects. Few studies evaluated the psychological outcomes. This system seems to be more effective than the first-generation automated insulin delivery systems. The MiniMed™ 780G has been associated with an improvement in sleep quality in subjects living with diabetes and their caregivers, along with an improvement in treatment satisfaction. Psychological distress is as reduced as the glucose control is improved. We also discuss some case reports describing particular situations in clinical practice. Finally, we think that data show that this system is a further step towards the improvement of the treatment of diabetes as concerns both metabolic and psychological outcomes.

Performance of Tandem Control IQ During Outdoor Physical Activity in Children and Adolescents with Type 1 Diabetes.

Background: Few data are available in children with type 1 diabetes using automated insulin delivery systems during physical activity (PA). We evaluated the time in range (TIR) during 2-h of outdoor PA in children using t:slim X2 with Control-IQ® technology. Materials and Methods: Caucasian children and adolescents, aged 9-18 years using t:slim X2 with Control-IQ technology were recruited during a local sporting event. Participants were divided into two groups: Group A practiced endurance activities for 60 min (1000-meter run, a jump circuit) and then power activities for 60 min (80-meter run, long jump); Group B practiced power activities for 60 min and then followed by endurance activities for 60 min. Ninety minutes before the PA, participants had lunch and self-administered a low-dose insulin, reduced by 50% compared to their regularly calculated meal dose per pump calculator. DexcomG6® data were downloaded. Results: Twenty-six children were recruited, 2 refused PA. Participants were divided as follows: 13 in Group A (7 males, median age 14.6 years) and 11 in Group B (8 males, median age 13.5 year). The mean glucose level when PA started was similar between groups (P = 0.06). Subjects in Group B showed a higher TIR than those in Group A ([50.4%, 95% confidence interval, CI: 33.8-75] vs. 39.6% [95% CI: 26.9-58.3], respectively [P = 0.39]). A significantly better TIR in Group B (53.8%, 95% CI: 30.2-96.1) compared to Group A (17.4%, 95% CI: 7.3-41.7, P = 0.02) was recorded during the first session. During the second session, TIR increased in both groups. There were no episodes of serious or severe hypoglycemia. Conclusions: No serious or severe hypoglycemic episodes were recorded during PA performed 90 min after lunch. Future studies using t:slim X2 with Control-IQ technology are necessary.

Chrononutrition and metabolic health in children and adolescents: a systematic review and meta-analysis.

CONTEXT: Obesity has emerged as a global health issue for the pediatric population, increasing the need to investigate physiopathological aspects to prevent the appearance of its cardiometabolic complications. Chrononutrition is a field of research in nutritional sciences that investigates the health impact of 3 different dimensions of feeding behavior: regularity of meals, frequency, and timing of food intake. OBJECTIVE: We carried out a systematic review and meta-analysis to investigate the association between chrononutrition in children and adolescents and the risk of overweight/obesity or a cluster of metabolic abnormalities related to glucose and lipid metabolism, blood pressure, and cardiovascular disease risk. DATA EXTRACTION: A literature search was performed using PubMed, EMBASE, and The Cochrane Library for relevant articles published before August 2022. DATA ANALYSIS: A total of 64 articles were included in the narrative synthesis (47 cross-sectional and 17 cohort studies), while 16 studies were included in the meta-analysis. Meta-analysis showed that non-daily breakfast consumers (≤6 d/wk) had a higher risk of overweight/obesity (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.08-1.82] compared with daily breakfast eaters (7 d/wk). Similarly, irregular breakfast consumption (only 0-to-3 times/wk) increased the risk of abdominal obesity (waist-to-height ratio ≥ 0.5) compared with regular consumption (5-to-7 times/wk) (OR, 1.38; 95% CI, 1.26-1.49). There was evidence to suggest that a regular frequency of meal consumption (≥4 times/d) is preventive against overweight/obesity development compared with fewer meals (≤3 times/d) (OR, 0.83; 95% CI, 0.70-0.97). In the narrative synthesis, snacking habits showed controversial results, while food timing was the most understudied dimension. CONCLUSION: Overall, our data indicate a potential implication of chrononutrition in affecting pediatric metabolic health; however, the evidence of this association is limited and heterogeneous. Further prospective and intervention studies with a consistent approach to categorize the exposure are needed to elucidate the importance of chrononutrition for pediatric metabolic health.

Early lung diffusion abnormalities and airways' inflammation in children with type 1 diabetes.

BACKGROUND AND AIMS OF THE STUDY: Type 1 diabetes (T1D) impacts lung function and exercise capacity in adults, but limited information is available in children. We hypothesize that T1D causes alterations in pulmonary function and cardiorespiratory fitness, i.e., exercise capacity, at early stages of the disease, due to the presence of inflammation and vascular damage. Therefore, we aim to investigate pulmonary function before and after exercise in children with T1D as compared to age matched healthy controls. METHOD: Twenty-four children with T1D and twenty healthy controls underwent body plethysmography, diffusion lung capacity for carbon monoxide and fractional exhaled nitric oxide at rest and after cardio-pulmonary exercise test. RESULTS: In children with T1D, baseline total lung capacity and diffusion lung capacity for carbon monoxide were reduced as compared to healthy controls. Children with T1D also showed a reduced exercise capacity associated with poor aerobic fitness. Accordingly, diffusion lung capacity for carbon monoxide tended to increase with exercise in healthy controls, while no change was observed in children with T1D. Fractional exhaled nitric oxide was significantly higher at baseline and tended to increase with exercise in children with T1D, while no changes were observed in healthy controls. CONCLUSIONS: Altered diffusion lung capacity for carbon monoxide, increased fractional exhaled nitric oxide and a poor aerobic fitness to exercise suggests the presence of early pulmonary abnormalities in children with T1D.

Prioritizing educational initiatives on emerging technologies for Italian pediatricians: bibliometric review and a survey.

BACKGROUND: Emerging technologies have demonstrated outstanding potential in improving healthcare, yet their full integration remains a challenge for all medical specialties, including pediatrics. To support the swift implementation of technologies, we identified the current trends through a bibliometric review, and we conducted a survey on Italian pediatricians to gauge educational needs and willingness to integrate technologies into clinical practice. METHODS: A working group of pediatricians representing various backgrounds designed and coordinated the study. To identify relevant topics for educational strategy development, we focused on virtual reality, telehealth, natural language processing, smartphone applications, robotics, genomics, and artificial intelligence. A bibliometric analysis limited to 2018-2023 was performed to identify trends and emerging applications within each topic. Based on the results, a questionnaire was developed and made available online to all Italian pediatricians. The results were analyzed through descriptive analysis and a multivariable logistic regression to explore associations between technology adoption and sociodemographic characteristics. RESULTS: A total of 3,253 publications were found, with Telehealth and Telemedicine having the highest number of publications and Natural Language Processing the lowest. The number of respondents to the online questionnaire was 1,540, predominantly medical doctors with over 20 years of experience working as family pediatricians. Telehealth had the highest level of knowledge (95.2%), followed by smartphone applications (89.1%) and genomics (63.2%). The greatest potential for increased use through education programs was projected for natural language processing (+ 43.1%), artificial intelligence (+ 39.6%), and virtual and mixed reality (+ 38.1%). Female respondents and older individuals were less likely to use emerging technologies. Hospital pediatricians and residents were more likely to use AI. CONCLUSIONS: We developed a replicable strategy to identify emerging themes in medical technologies relevant to pediatrics and assess the educational needs of pediatricians. A significant gap still exists between current and potential usage of emerging technologies among Italian pediatricians although they showed a positive attitude towards implementing these technologies following specific education programs. The study highlights the need for comprehensive education programs on emerging technologies in pediatrics and recommends addressing gender and age disparities in technology adoption.

Leading reasons for antibiotic prescriptions in pediatric respiratory infections: influence of fever in a primary care setting.

BACKGROUND: Antibiotic overuse in children is a significant public health concern, as it can lead to the emergence and spread of antibiotic-resistant bacteria. Although respiratory infections account for most antibiotic prescriptions in children, many of these infections are viral and do not require antibiotics. In this study, we aimed to investigate the use of antibiotics in children with respiratory infections in a primary care setting and to explore the possible role of fever on antibiotic prescription. METHODS: We conducted a prospective observational study that evaluated preschool children aged 0-5 years who were assessed by their primary care pediatricians for respiratory infectious diseases between October 2019 and March 2021. The study involved 69 public primary care pediatricians and a total of 678 pediatric episodes for respiratory infections. RESULTS: Amoxicillin/clavulanate was the most frequently prescribed drug. Bronchitis accounted for most of inappropriate antibiotic prescriptions (73%). Furthermore, the presence of fever was associated with a ~ 300% increase in the likelihood of prescribing antibiotics for respiratory infections that do not typically require antibiotics. CONCLUSION: Our findings emphasize the need for adherence to international guidelines and recommendations in the primary care of children to reduce unnecessary antibiotic use and prevent the development of antibiotic resistance. This study also underscores the potential relevance of new studies to evaluate antibiotic prescription attitudes in other clinical settings and geographical areas.

New therapies towards a better glycemic control in youths with type 1 diabetes.

Type 1 diabetes (T1D) is the most frequent form of diabetes in pediatric age, affecting more than 1.5 million people younger than age 20 years worldwide. Early and intensive control of diabetes provides continued protection against both microvascular and macrovascular complications, enhances growth, and ensures normal pubertal development. In the absence of definitive reversal therapy for this disease, achieving and maintaining the recommended glycemic targets is crucial. In the last 30 years, enormous progress has been made using technology to better treat T1D. In spite of this progress, the majority of children, adolescents and young adults do not reach the recommended targets for glycemic control and assume a considerable burden each day. The development of promising new therapeutic advances, such as more physiologic insulin analogues, pioneering diabetes technology including continuous glucose monitoring and closed loop systems as well as new adjuvant drugs, anticipate a new paradigm in T1D management over the next few years. This review presents insights into current management of T1D in youths.

Lessons and gaps in the prediction and prevention of type 1 diabetes.

Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the root cause of T1D development has yet to be determined, enough is known about the natural history of T1D pathogenesis to allow study of interventions that may delay or even prevent the onset of hyperglycemia and clinical T1D. Primary prevention aims to prevent the onset of beta cell autoimmunity in asymptomatic people at high genetic risk for T1D. Secondary prevention strategies aim to preserve functional beta cells once autoimmunity is present, and tertiary prevention aims to initiate and extend partial remission of beta cell destruction after the clinical onset of T1D. The approval of teplizumab in the United States to delay the onset of clinical T1D marks an impressive milestone in diabetes care. This treatment opens the door to a paradigm shift in T1D care. People with T1D risk need to be identified early by measuring T1D related islet autoantibodies. Identifying people with T1D before they have symptoms will facilitate better understanding of pre-symptomatic T1D progression and T1D prevention strategies that may be effective.

Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.

We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.

Alteration of taste perception, food neophobia and oral microbiota composition in children with food allergy.

Currently, the mechanisms underlying sensory perception and sensory performance in children with food allergies are far from being understood. As well, only recently, single research afforded the oral host-commensal milieu, addressing oral microbial communities in children with peanut allergies. To bridge the current gaps in knowledge both in the sensory and microbial fields, a psychophysiological case-control study was performed in allergic children (n = 29) and a healthy sex-age-matched control group (n = 30). Taste perception, food neophobia, and liking were compared in allergic and non-allergic children. The same subjects were characterized for their oral microbiota composition by addressing saliva to assess whether specific profiles were associated with the loss of oral tolerance in children with food allergies. Our study evidenced an impaired ability to correctly identify taste qualities in the allergic group compared to controls. These results were also consistent with anatomical data related to the fungiform papillae on the tongue, which are lower in number in the allergic group. Furthermore, distinct oral microbial profiles were associated with allergic disease, with significant down-representations of the phylum Firmicutes and of the genera Veillonella spp., Streptococcus spp., Prevotella spp., and Neisseria spp. For the first time, this study emphasizes the link between sensory perception and food allergy, which is a novel and whole-organism view of this pathology. Our data indicated that an impaired taste perception, as regards both functionality and physiologically, was associated with food allergy, which marginally influences the food neophobia attitude. It is also accompanied by compositional shifts in oral microbiota, which is, in turn, another actor of this complex interplay and is deeply interconnected with mucosal immunity. This multidisciplinary research will likely open exciting new approaches to therapeutic interventions.

Safety, metabolic and psychological outcomes of Medtronic MiniMed 670G in children, adolescents and young adults: a systematic review.

Hybrid closed loop (HCL) systems are the combination of a pump for insulin delivery and a glucose sensor for continuous glucose monitoring. These systems are managed by an algorithm, which delivers insulin on the basis of the interstitial glucose levels. The MiniMed™ 670G system was the first HCL system available for clinical purpose. In this paper, we reviewed the literature about metabolic and psychological outcomes in children, adolescents and young adults with type 1 diabetes treated with MiniMed™ 670G. Only 30 papers responded to the inclusion criteria and thus were considered. All the papers show that the system is safe and effective in managing glucose control. Metabolic outcomes are available up to 12 months of follow-up; longer study period are lacking. This HCL system may improve HbA1c up to 7.1% and time in range up to 73%. The time spent in hypoglycaemia is almost neglectable. Better improvement in blood glucose control is observed in patients with higher HbA1c at HCL system start and larger daily use of auto-mode functionality.     Conclusion: The Medtronic MiniMed™ 670G is safe and well accepted, without any increase in the burden for patients. Some papers report an improvement in the psychological outcomes, but other papers do not confirm this finding. So far, it significantly improves the management of diabetes mellitus in children, adolescents and young adults. Proper training and support by the diabetes team are mandatory. Studies for a period longer than 1 year would be appreciated to better understand the potentiality of this system. What is Known: • The Medtronic MiniMedTM 670G is a hybrid closed loop system which combines a continuous glucose monitoring sensor with an insulin pump. • It has been the first hybrid closed loop system available for clinical purpose. Adequate training and patients support play a key role in diabetes management. What is New: • The Medtronic MiniMedTM 670G may improve HbA1c and CGM metrics up to 1-year of follow-up, but the improvement appears lower than advanced hybrid closed loop systems. This system is effective to prevent hypoglycaemia. • The psychosocial effects remain less understood in terms of improvement of psychosocial outcomes. The system has been considered to provide flexibility and independence by the patients and their caregivers. The workload required to use this system is perceived as a burden by the patients who decrease the use of auto-mode functionality over time.

Lipodystrophies in non-insulin-dependent children: Treatment options and results from recombinant human leptin therapy.

Lipodystrophy is a general definition containing different pathologies which, except for those observed in insulin-treated subjects falling outside the scope of this paper, are characterized by total or partial lack of body fat, that, according to the amount of missing adipose tissue, are divided in generalized or partial lipodystrophy. These diseases are characterized by leptin deficiency, which often leads to metabolic derangement, causing insulin resistance, dyslipidemia, and increasing cardiovascular risk. In this narrative review, we presentend the clinical presentation of different types of lipodystrophies and metabolic unbalances related to disease in children and adolescents, focusing on the main treatment options and the novel results from recombinant human leptin (metreleptin) therapy. Milestones in the management of lipodystrophy include lifestyle modification as diet and physical activity, paired with hypoglycemic drugs, insulin, hypolipidemic drugs, and other drugs with the aim of treating lipodystrophy complications. Metreleptin has been recently approved for pediatric patients with general lipodystrophy (GL)> 2 years of age and for children with partial lipodystrophy (PL)> 12 years of age not controlled with conventional therapies. New therapeutic strategies are currently being investigated, especially for patients with PL forms, specifically, liver-targeted therapies. Further studies are needed to achieve the most specific and precise treatment possible.

What we know about the relationship between autoimmune thyroid diseases and gut microbiota: a perspective on the role of probiotics on pediatric endocrinology.

INTRODUCTION: Autoimmune diseases account for a cumulative overall prevalence of about 3-5% worldwide. Among them, autoimmune thyroid diseases (ATDs) are the most common and comprise two main entities: Hashimoto's thyroiditis (HT) and Graves-Basedow disease (GD). The pathogenesis of ATDs remains not fully elucidated, however the role of microbioma has been proposed. Gut microbiota exert an important influence on the intestinal barrier, nutrient metabolism and immune system development and functions. EVIDENCE ACQUISITION: In this review, we describe on the main features of ATDs in pediatrics, focusing on the reciprocal influence between gut microbiota, thyroid hormone metabolism and thyroid autoimmunity and consider the role of probiotics and other microbiota-targeted therapies in thyroid diseases with a perspective on pediatric endocrinology. EVIDENCE SYNTHESIS: Microbiome affects both endogenous and exogenous thyroid hormone metabolism and influences the absorption of minerals important to the thyroid function, which are iodine, selenium, zinc and iron. The alteration of the gut microbiota, with the consequent modifications in the barrier function and the increased gut permeability, seems involved in the development of autoimmune and chronic inflammatory diseases, including ATDs. The supplementation with probiotics showed beneficial effects on the thyroid hormone and thyroid function because this strategy could restore the intestinal eubiosis and the good strain microorganism proliferation. CONCLUSIONS: Even though the evidence about the interaction between microbiota and ATDs in pediatric patients is limited, the promising results obtained in the adult population, and in other autoimmune disorders affecting children, highlight the need of for further research in the pediatric field.